tbuckley/cabot-search huggingface dataset:
Cetuximab for the Treatment of Colorectal Cancer
Authors: Derek J. Jonker, Chris J. O'Callaghan, Christos S. Karapetis, John R. Zalcberg, Dongsheng Tu, Heather-Jane Au, Scott R. Berry, Marianne Krahn, Timothy Price, R. John Simes, Niall C. Tebbutt, Guy van Hazel, Rafal Wierzbicki, Christiane Langer, Malcolm J. Moore
Journal: New England Journal of Medicine (2007)

Cetuximab, an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor (EGFR), has activity against colorectal cancers that express EGFR.
Trends in HIV prevalence, incidence, and progress towards the UNAIDS 95-95-95 targets in Malawi among individuals aged 15–64 years: population-based HIV impact assessments, 2015−16 and 2020−21
Authors: Danielle Payne, Nellie Wadonda-Kabondo, Alice Wang, Joshua Smith-Sreen, Alinune Kabaghe, George Bello, Felix Kayigamba, Lyson Tenthani, Alice Maida, Andrew Auld, Andrew C Voetsch, Sasi Jonnalagadda, Kristin Brown, Christine A West, Evelyn Kim, Francis Ogollah, Mansoor Farahani, Trudy Dobbs, Andreas Jahn, Kelsey Mirkovic, Rose Nyirenda, Charles Mwansambo, Thokozani Kalua, Mathews Kagoli, Bernard Mvula, Mercy Kanyuka, Jameson Ndawala, Isaac Chirwa, Blackson Matatiyo, Daniel Yavo, Hetal Patel, Bharat Parekh, Wafaa El-Sadr, Duncan Chege, Elizabeth Radin, David Hoos, Andrea Low, Elizabeth Gummerson
Journal: The Lancet HIV (2023)
Integrated Multimodal Analyses of DNA Damage Response and Immune Markers as Predictors of Response in Metastatic Triple-Negative Breast Cancer in the TNT Trial (NCT00532727)
Authors: Holly Tovey, Orsolya Sipos, Joel S. Parker, Katherine A. Hoadley, Jelmar Quist, Sarah Kernaghan, Lucy Kilburn, Roberto Salgado, Sherene Loi, Richard D. Kennedy, Ioannis Roxanis, Patrycja Gazinska, Sarah E. Pinder, Judith Bliss, Charles M. Perou, Syed Haider, Anita Grigoriadis, Andrew Tutt, Maggie Chon U. Cheang
Journal: Clinical Cancer Research (2023)

Abstract Purpose: The TNT trial (NCT00532727) showed no evidence of carboplatin superiority over docetaxel in metastatic triple-negative breast cancer (mTNBC), but carboplatin benefit was observed in the germline BRCA1/2 mutation subgroup. Broader response-predictive biomarkers are needed. We explored the predictive ability of DNA damage response (DDR) and immune markers. Experimental Design: Tumor-infiltrating lymphocytes were evaluated for 222 of 376 patients. Primary tumors (PT) from 186 TNT participants (13 matched recurrences) were profiled using total RNA sequencing. Four transcriptional DDR-related and 25 immune-related signatures were evaluated. We assessed their association with objective response rate (ORR) and progression-free survival (PFS). Conditional inference forest clustering was applied to integrate multimodal data. The biology of subgroups was characterized by 693 gene expression modules and other markers. Results: Transcriptional DDR-related biomarkers were not predictive of ORR to either treatment overall. Changes from PT to recurrence were demonstrated; in chemotherapy-naïve patients, transcriptional DDR markers separated carboplatin responders from nonresponders (P values = 0.017; 0.046). High immune infiltration was associated with docetaxel ORR (interaction P values &amp;lt; 0.05). Six subgroups were identified; the immune-enriched cluster had preferential docetaxel response [62.5% (D) vs. 29.4% (C); P = 0.016]. The immune-depleted cluster had preferential carboplatin response [8.0% (D) vs. 40.0% (C); P = 0.011]. DDR-related subgroups were too small to assess ORR. Conclusions: High immune features predict docetaxel response, and high DDR signature scores predict carboplatin response in treatment-naïve mTNBC. Integrating multimodal DDR and immune-related markers identifies subgroups with differential treatment sensitivity. Treatment options for patients with immune-low and DDR-proficient tumors remains an outstanding need. Caution is needed using PT-derived transcriptional signatures to direct treatment in mTNBC, particularly DDR-related markers following prior chemotherapy.
Integration of MyD88 inhibitor into mesoporous cerium oxide nanozymes-based targeted delivery platform for enhancing treatment of ulcerative colitis
Authors: Hongbing Liu, Muse Ji, Yuti Bi, Peifu Xiao, Jiansong Zhao, Jingxin Gou, Tian Yin, Haibing He, Huaiwei Ding, Xing Tang, Yu Zhang
Journal: Journal of Controlled Release (2023)
DICER1 Mutations Do Not Always Indicate Dismal Prognosis in Pediatric Poorly Differentiated Thyroid Carcinomas
Authors: Gülçin Yegen, Ali Yılmaz Altay, İsmail Yılmaz, Yalın İşcan, İsmail Cem Sormaz, Nihat Aksakal, Semen Önder, Özgür Mete
Journal: Endocrine Pathology (2023)
Proteogenomic data and resources for pan-cancer analysis
Authors: Yize Li, Yongchao Dou, Felipe Da Veiga Leprevost, Yifat Geffen, Anna P. Calinawan, François Aguet, Yo Akiyama, Shankara Anand, Chet Birger, Song Cao, Rekha Chaudhary, Padmini Chilappagari, Marcin Cieslik, Antonio Colaprico, Daniel Cui Zhou, Corbin Day, Marcin J. Domagalski, Myvizhi Esai Selvan, David Fenyö, Steven M. Foltz, Alicia Francis, Tania Gonzalez-Robles, Zeynep H. Gümüş, David Heiman, Michael Holck, Runyu Hong, Yingwei Hu, Eric J. Jaehnig, Jiayi Ji, Wen Jiang, Lizabeth Katsnelson, Karen A. Ketchum, Robert J. Klein, Jonathan T. Lei, Wen-Wei Liang, Yuxing Liao, Caleb M. Lindgren, Weiping Ma, Lei Ma, Michael J. MacCoss, Fernanda Martins Rodrigues, Wilson McKerrow, Ngoc Nguyen, Robert Oldroyd, Alexander Pilozzi, Pietro Pugliese, Boris Reva, Paul Rudnick, Kelly V. Ruggles, Dmitry Rykunov, Sara R. Savage, Michael Schnaubelt, Tobias Schraink, Zhiao Shi, Deepak Singhal, Xiaoyu Song, Erik Storrs, Nadezhda V. Terekhanova, Ratna R. Thangudu, Mathangi Thiagarajan, Liang-Bo Wang, Joshua M. Wang, Ying Wang, Bo Wen, Yige Wu, Matthew A. Wyczalkowski, Yi Xin, Lijun Yao, Xinpei Yi, Hui Zhang, Qing Zhang, Maya Zuhl, Gad Getz, Li Ding, Alexey I. Nesvizhskii, Pei Wang, Ana I. Robles, Bing Zhang, Samuel H. Payne, Alexander J. Lazar, Amanda G. Paulovich, Antonio Colaprico, Antonio Iavarone, Arul M. Chinnaiyan, Brian J. Druker, Chandan Kumar-Sinha, Chelsea J. Newton, Chen Huang, D.R. Mani, Richard D. Smith, Emily Huntsman, Eric E. Schadt, Eunkyung An, Francesca Petralia, Galen Hostetter, Gilbert S. Omenn, Hanbyul Cho, Henry Rodriguez, Hui Zhang, Iga Kolodziejczak, Jared L. Johnson, Jasmin Bavarva, Jimin Tan, Karin D. Rodland, Karl R. Clauser, Karsten Krug, Lewis C. Cantley, Maciej Wiznerowicz, Matthew J. Ellis, Meenakshi Anurag, Mehdi Mesri, Michael A. Gillette, Michael J. Birrer, Michele Ceccarelli, Saravana M. Dhanasekaran, Nathan Edwards, Nicole Tignor, Özgün Babur, Pietro Pugliese, Sara J.C. Gosline, Scott D. Jewell, Shankha Satpathy, Shrabanti Chowdhury, Stephan Schürer, Steven A. Carr, Tao Liu, Tara Hiltke, Tomer M. Yaron, Vasileios Stathias, Wenke Liu, Xu Zhang, Yizhe Song, Zhen Zhang, Daniel W. Chan
Journal: Cancer Cell (2023)

The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigates tumors from a proteogenomic perspective, creating rich multi-omics datasets connecting genomic aberrations to cancer phenotypes. To facilitate pan-cancer investigations, we have generated harmonized genomic, transcriptomic, proteomic, and clinical data for >1000 tumors in 10 cohorts to create a cohesive and powerful dataset for scientific discovery. We outline efforts by the CPTAC pan-cancer working group in data harmonization, data dissemination, and computational resources for aiding biological discoveries. We also discuss challenges for multi-omics data integration and analysis, specifically the unique challenges of working with both nucleotide sequencing and mass spectrometry proteomics data.
Symbiotic Firmicutes establish mutualism with the host via innate tolerance and resistance to control systemic immunity
Authors: Christine K.I. Jordan, Rebecca L. Brown, Max L.Y. Larkinson, Richard P. Sequeira, Andrew M. Edwards, Thomas B. Clarke
Journal: Cell Host & Microbe (2023)

The intestinal microbiota regulates immunity across organ systems. Which symbionts control systemic immunity, the mechanisms they use, and how they avoid widespread inflammatory damage are unclear. We uncover host tolerance and resistance mechanisms that allow Firmicutes from the human microbiota to control systemic immunity without inducing immunopathology. Intestinal processing releases Firmicute glycoconjugates that disseminate, resulting in release of cytokine IL-34 that stimulates macrophages and enhances defenses against pneumonia, sepsis, and meningitis. Despite systemic penetration of Firmicutes, immune homeostasis is maintained through feedback control whereby IL-34-mediated mTORC1 activation in macrophages clears polymeric glycoconjugates from peripheral tissues. Smaller glycoconjugates evading this clearance mechanism are tolerated through sequestration by albumin, which acts as an inflammatory buffer constraining their immunological impact. Without these resistance and tolerance mechanisms, Firmicutes drive catastrophic organ damage and cachexia via IL-1β. This reveals how Firmicutes are safely assimilated into systemic immunity to protect against infection without threatening host viability.
Management of Ductal Carcinoma In Situ of the Breast
Authors: Chirag Shah, Jessica Wobb, Bindu Manyam, Neilendu Kundu, Douglas Arthur, David Wazer, Eduardo Fernandez, Frank Vicini
Journal: JAMA Oncology (2016)

<h3>Importance</h3> Ductal carcinoma in situ (DCIS) of the breast represents a disease process that continues to increase in incidence with treatment paradigms that continue to evolve. Greater access to long-term data from large observational studies addressing the natural history of the disease has contributed to changes in treatment paradigms and put into question traditional management strategies. <h3>Observations</h3> While recent analyses have suggested that a more conservative approach to the management of DCIS without surgical intervention or radiation therapy may be advisable based on breast cancer mortality data, there is a lack of level 1 or prospective evidence to support the widespread adoption of these approaches. Currently, surgery remains the standard of care for the initial treatment of DCIS. Adjuvant radiation therapy (RT) has consistently demonstrated a reduction in the risk of local recurrence following breast-conserving surgery (BCS), even in "low-risk" populations of patients. Invasive recurrences following BCS are associated with increases in breast cancer mortality. Questions that remain to be answered include (1) what constitutes an acceptable risk of local recurrence, (2) what are the costs associated with managing local recurrences compared with RT given initially after BCS (particularly in light of data supporting shorter courses of RT), and (3) what are the benefits of endocrine therapy on local recurrence, and do they justify the additional toxic effects and potential noncompliance with their long-term administration? <h3>Conclusions and Relevance</h3> Surgery and RT remain standard of care treatment options in the management of DCIS. Future studies are required to identify cohorts of patients in which RT can be safely omitted as well as to evaluate whether short-course RT alone may represent a better option than endocrine therapy with respect to compliance, toxic effects, cost and local control following BCS.
Phase IV head-to-head randomized controlled trial comparing ingenol mebutate 0·015% gel with diclofenac sodium 3% gel for the treatment of actinic keratosis on the face or scalp
Authors: E. Stockfleth, C.A. Harwood, C. Serra-Guillén, T. Larsson, M.L. Østerdal, T. Skov
Journal: British Journal of Dermatology (2017)

Ingenol mebutate (IngMeb) and diclofenac sodium (DS) are approved treatments for actinic keratosis (AK). To compare the efficacy and safety of IngMeb 0·015% gel with DS 3% gel (NCT02406014). Patients with 4–8 visible, discrete AK lesions on the face/scalp in a 25 cm2 contiguous area of skin were randomized 1:1 to IngMeb once‐daily for three consecutive days or DS twice‐daily for 90 days. Patients with AK lesions at Week 8 following IngMeb were offered a second IngMeb course. Primary end point was complete clearance of AK lesions (AKCLEAR 100) at end of first treatment course (Week 8, IngMeb; Week 17, DS). Secondary end points included AKCLEAR 100 at end of last treatment course and Week 17; adverse events (AEs) were assessed at these time points. Patients completed treatment satisfaction questionnaires for medication (TSQM; Week 17). AKCLEAR 100 at end of first treatment course was higher with IngMeb (34%) vs. DS (23%; P = 0·006). AKCLEAR 100 at end of last IngMeb course (53%) and Week 17 (45%) was higher than DS (both P < 0·001). The most frequent AE was application‐site erythema (IngMeb 19%; DS 12%). Treatment‐related AE (TRAE) duration was shorter with IngMeb. TRAE withdrawals were lower for IngMeb (2%) vs. DS (6%). TSQM scores for global satisfaction (P < 0·001) and effectiveness (P = 0·002) were higher with IngMeb, as was dosing instruction adherence (≥ 90% vs. 70%). AKCLEAR 100, patient treatment satisfaction and effectiveness were significantly higher with IngMeb compared with DS, demonstrating superiority of IngMeb for AK treatment on face/scalp.
Retraction Note: HNF4A-AS1/hnRNPU/CTCF axis as a therapeutic target for aerobic glycolysis and neuroblastoma progression
Authors: Huajie Song, Dan Li, Xiaojing Wang, Erhu Fang, Feng Yang, Anpei Hu, Jianqun Wang, Yanhua Guo, Yang Liu, Hongjun Li, Yajun Chen, Kai Huang, Liduan Zheng, Qiangsong Tong
Journal: Journal of Hematology & Oncology (2023)
New biologic (Ab-IPL-IL-17) for IL-17-mediated diseases: identification of the bioactive sequence (nIL-17) for IL-17A/F function
Authors: Anella Saviano, Adel Abo Manosour, Federica Raucci, Francesco Merlino, Noemi Marigliano, Anna Schettino, Mussarat Wahid, Jenefa Begum, Andrew Filer, Julia E Manning, Gian Marco Casillo, Marialuisa Piccolo, Maria Grazia Ferraro, Simona Marzano, Pasquale Russomanno, Rosa Bellavita, Carlo Irace, Jussara Amato, Mohammed Alfaifi, Peter Rimmer, Tariq Iqbal, Stefano Pieretti, Valentina Vellecco, Francesco Caso, Luisa Costa, Roberto Giacomelli, Raffaele Scarpa, Giuseppe Cirino, Mariarosaria Bucci, Helen M McGettrick, Paolo Grieco, Asif Jilani Iqbal, Francesco Maione
Journal: Annals of the Rheumatic Diseases (2023)

Objectives Interleukin (IL) 17s cytokines are key drivers of inflammation that are functionally dysregulated in several human immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis (RA), psoriasis and inflammatory bowel disease (IBD). Targeting these cytokines has some therapeutic benefits, but issues associated with low therapeutic efficacy and immunogenicity for subgroups of patients or IMIDs reduce their clinical use. Therefore, there is an urgent need to improve the coverage and efficacy of antibodies targeting IL-17A and/or IL-17F and IL-17A/F heterodimer. Methods and results Here, we initially identified a bioactive 20 amino acid IL-17A/F-derived peptide (nIL-17) that mimics the pro-inflammatory actions of the full-length proteins. Subsequently, we generated a novel anti-IL-17 neutralising monoclonal antibody (Ab-IPL-IL-17) capable of effectively reversing the pro-inflammatory, pro-migratory actions of both nIL-17 and IL-17A/F. Importantly, we demonstrated that Ab-IPL-IL-17 has less off-target effects than the current gold-standard biologic, secukinumab. Finally, we compared the therapeutic efficacy of Ab-IPL-IL-17 with reference anti-IL-17 antibodies in preclinical murine models and samples from patients with RA and IBD. We found that Ab-IPL-IL-17 could effectively reduce clinical signs of arthritis and neutralise elevated IL-17 levels in IBD patient serum. Conclusions Collectively, our preclinical and in vitro clinical evidence indicates high efficacy and therapeutic potency of Ab-IPL-IL-17, supporting the rationale for large-scale clinical evaluation of Ab-IPL-IL-17 in patients with IMIDs.
Bone Regeneration in a Large Animal Model Featuring a Modular Off‐the‐Shelf Soft Callus Mimetic
Authors: Leanne de Silva, Alessia Longoni, Flurina Staubli, Silke Nurmohamed, Anneli Duits, Antoine J. W. P. Rosenberg, Debby Gawlitta
Journal: Advanced Healthcare Materials (2023)

Implantation of engineered cartilage with soft callus features triggers remodeling to bone tissue via endochondral bone regeneration (EBR). Thus far, EBR has not progressed to the level of large animals on the axis of clinical translation. Herein, the feasibility of EBR is aimed for a critical-sized defect in a large animal model. Chondrogenesis is first induced in goat-derived multipotent mesenchymal stromal cells (MSCs) by fine-tuning the cellular differentiation process. Through a unique devitalization process, two off-the-shelf constructs aimed to recapitulate the different stages of the transient cartilaginous soft callus template in EBR are generated. To evaluate bone regeneration, the materials are implanted in an adapted bilateral iliac crest defect model in goats, featuring a novel titanium star-shaped spacer. After 3 months, the group at the more advanced differentiation stage shows remarkable regenerative capacity, with comparable amounts of bone regeneration as the autograft group. In contrast, while the biomaterial mimicking the earlier stages of chondrogenesis shows improved regeneration compared to the negative controls, this is subpar compared to the more advanced material. Concluding, EBR is attainable in large animals with a soft callus mimetic material that leads to fast conversion into centimeter-scale bone, which prospects successful implementation in the human clinics.
Principles to Advance Value in Inflammatory Bowel Disease: A Collaborative Payer-Provider Framework
Authors: Joel Ang, Paul Berggreen, Joseph Couto, Lindee Goh, Emma Hoo, David Johnson, Laurie Keefer, Lawrence Kosinski, Philip Krebs, Joseph O’Hara, Luke Prettol, Corey Siegel, Elizabeth Shaughnessy
Journal: Clinical Gastroenterology and Hepatology (2023)
Development and validation of a mutation-annotated prognostic score for intrahepatic cholangiocarcinoma after resection: a retrospective cohort study
Authors: Xiang-Yu Wang, Wen-Wei Zhu, Lu Lu, Yi-Tong Li, Ying Zhu, Lu-Yu Yang, Hao-Ting Sun, Chao-Qun Wang, Jing Lin, Chong Huang, Xin Yang, Jie Fan, Hu-Liang Jia, Ju-Bo Zhang, Bao-Bing Yin, Jin-Hong Chen, Lun-Xiu Qin
Journal: International Journal of Surgery (2023)

The value of existing prognostic models for intrahepatic cholangiocarcinoma is limited. The inclusion of prognostic gene mutations would enhance the predictive efficacy.In the screening cohorts, univariable Cox regression analysis was applied to investigate the effect of individual mutant genes on overall survival (OS). In the training set, multivariable analysis was performed to evaluate the independent prognostic roles of the clinicopathological and mutational parameters, and a prognostic model was constructed. Internal and external validations were conducted to evaluate the performance of this model.Among the recurrent mutations, only TP53 and KRASG12 were significantly associated with OS across all three screening cohorts. In the training cohort, TP53 and KRASG12 mutations in combination with seven other clinical parameters (tumor size, tumor number, vascular invasion, lymph node metastasis, adjacent invasion, CA19-9, and CEA), were independent prognostic factors for OS. A mutation-annotated prognostic score (MAPS) was established based on the nine prognosticators. The C-indices of MAPS (0.782 and 0.731 in the internal and external validation cohorts, respectively) were statistically higher than those of other existing models ( P <0.05). Furthermore, the MAPS model also demonstrated significant value in predicting the possible benefits of upfront surgery and adjuvant therapy.The MAPS model demonstrated good performance in predicting the OS of intrahepatic cholangiocarcinoma patients. It may also help predict the possible benefits of upfront surgery and adjuvant therapy.
The predictive role of hematologic markers in resectable NSCLC patients treated with neoadjuvant chemoimmunotherapy: a retrospective cohort study
Authors: Wenliang Liu, Siying Ren, Lulu Yang, Ying Xiao, Chao Zeng, Chen Chen, Fang Wu, Yan Hu
Journal: International Journal of Surgery (2023)

Neoadjuvant chemoimmunotherapy is an important therapeutic modality for resectable nonsmall cell lung cancer (NSCLC). The roles of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio in predicting the efficacy and prognosis of patients with resectable NSCLC receiving neoadjuvant chemoimmunotherapy remain uncertain. This study aimed to explore the association of baseline and preoperative NLR, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio with the treatment response and survival of patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy.Data of patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy between May 2019 and July 2022 at our institute, were retrospectively analyzed. Peripheral blood cell counts were obtained at baseline and before surgery. Data that may affect treatment efficacy were also collected and analyzed, including age, sex, BMI, cumulative smoking exposure, pathological type, clinical stage, PD-L1 tumor proportion score, immune checkpoint inhibitors, dosage of neoadjuvant therapy, duration from final therapy to surgery, and baseline and preoperative oncological markers. The present work has been reported in compliance with REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria and guidelines (Supplemental Digital Content 1, http://links.lww.com/JS9/A860 ).A total of 116 patients were included in the study. Univariate logistic regression analysis showed that a higher baseline NLR ( P =0.001) and preoperative NLR ( P =0.001) were associated with a lower incidence of pathological complete response (pCR) following neoadjuvant therapy. Multivariate analysis indicated that a lower incidence of pCR was achieved in the high baseline NLR group ( P =0.014). Higher baseline NLR ( P =0.021), preoperative NLR ( P =0.004) and higher preoperative CEA levels ( P =0.059) were associated with shorter disease-free survival (DFS). Multivariate Cox proportional hazard regression analyses showed that shorter DFS was achieved in the high preoperative NLR group ( P =0.033).In patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy, a higher baseline NLR was associated with a lower incidence of pCR, and a higher preoperative NLR was associated with a shorter DFS. However, a future prospective study with a large sample size and long-term follow-up is needed to verify the predictive value of NLR in these patients.